| Autor: |
Kannan MP; Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical & Technical Sciences (SIMATS), Thandalam, Chennai, Tamil Nadu, 602105, India.; B-Aatral Biosciences Private Limited, Bangalore, Karnataka, 560091, India., Sreeraman S; Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical & Technical Sciences (SIMATS), Thandalam, Chennai, Tamil Nadu, 602105, India.; SRIIC Lab, Sri Ramachandra Institute for Higher Education & Research, Chennai, Tamil Nadu, 600116, India., Somala CS; B-Aatral Biosciences Private Limited, Bangalore, Karnataka, 560091, India., Kushwah RB; B-Aatral Biosciences Private Limited, Bangalore, Karnataka, 560091, India.; Department of Entomology and Agrilife Research, Texas A&M University, College Station, TX 77843, USA., Mani SK; B-Aatral Biosciences Private Limited, Bangalore, Karnataka, 560091, India.; Department of Biotechnology, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, 600073, India., Sundaram V; Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical & Technical Sciences (SIMATS), Thandalam, Chennai, Tamil Nadu, 602105, India., Thirunavukarasou A; B-Aatral Biosciences Private Limited, Bangalore, Karnataka, 560091, India.; SRIIC Lab, Sri Ramachandra Institute for Higher Education & Research, Chennai, Tamil Nadu, 600116, India. |
| Abstrakt: |
Targeted protein degradation (TPD) aids in developing novel bifunctional small-molecule degraders and eliminates proteins of interest. The TPD approach shows promising results in oncological, neurogenerative, cardiovascular and gynecological drug development. We provide an overview of technology advancements in TPD, including molecular glues, proteolysis-targeting chimeras (PROTACs), lysosome-targeting chimeras, antibody-based PROTAC, GlueBody PROTAC, autophagy-targeting chimera, autophagosome-tethering compound, autophagy-targeting chimera and chaperone-mediated autophagy-based degraders. Here we discuss the development and evolution of the TPD field, the variety of proteins that PROTACs target and the biological repercussions of their degradation. We particularly highlight the recent improvements in TPD research that utilize autophagy or the endolysosomal pathway, which enables the targeting of undruggable targets. |
